Bioartificial pulsatile cuffs fabricated from human induced pluripotent stem cell-derived cardiomyocytes using a pre-vascularization technique.

Bioartificial pulsatile cuffs fabricated from human induced pluripotent stem cell-derived cardiomyocytes using a pre-vascularization technique.
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DOI:
10.1038/s41536-022-00218-7
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发表时间:
2022-03-31
影响因子:
7.2
通讯作者:
Niinami H
Niinami H
中科院分区:
医学1区
文献类型:
--
作者:
Endo Y;Homma J;Sekine H;Matsuura K;Shimizu T;Niinami H

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有很大的兴趣在生物工程技术的发展搏动心肌组织作为下一代再生治疗严重心力衰竭。然而,用于再生医学的厚心肌移植物的创建需要并入血管。在这项研究中,我们描述了一种在体内构建血管网络的新方法,该方法允许从多层细胞片构建厚的人类心肌组织。将预先加载有生长因子的明胶片移植到大鼠的股浅动脉和静脉上。将这些结构一起封装在乙烯乙烯醇膜内,并在体内孵育3周(2周后结扎远端股浅动脉以促进血液流向血管床)。随后,分两个阶段将6个心肌细胞片移植到血管床上(3片,2次)。将该构建体再孵育一周,产生具有由适于与宿主血管吻合的动脉和静脉供应的独立循环的血管化人心肌组织。值得注意的是,在两个阶段而不是一个阶段将六个细胞层压在血管床上,可以产生更厚的心肌组织,同时抑制组织重塑和纤维化。最后,搏动的心肌组织被示出为当缠绕在大鼠的髂总动脉周围时产生辅助压力。这项技术的进一步发展可能有助于为心力衰竭患者制造循环辅助装置。
There is great interest in the development of techniques to bioengineer pulsatile myocardial tissue as a next-generation regenerative therapy for severe heart failure. However, creation of thick myocardial grafts for regenerative medicine requires the incorporation of blood vessels. In this study, we describe a new method of constructing a vascular network in vivo that allows the construction of thick human myocardial tissue from multi-layered cell sheets. A gelatin sheet pre-loaded with growth factors was transplanted onto the superficial femoral artery and vein of the rat. These structures were encapsulated together within an ethylene vinyl alcohol membrane and incubated in vivo for 3 weeks (with distal superficial femoral artery ligation after 2 weeks to promote blood flow to the vascular bed). Subsequently, six cardiomyocyte sheets were transplanted onto the vascular bed in two stages (three sheets, two times). Incubation of this construct for a further week generated vascularized human myocardial tissue with an independent circulation supplied by an artery and vein suitable for anastomosis to host vessels. Notably, laminating six cell sheets on the vascular bed in two stages rather than one allowed the creation of thicker myocardial tissue while suppressing tissue remodeling and fibrosis. Finally, the pulsatile myocardial tissue was shown to generate auxiliary pressure when wrapped around the common iliac artery of a rat. Further development of this technique might facilitate the generation of circulatory assist devices for patients with heart failure.
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